Effects of L-2-oxothiazolidine-4-carboxylate, a cysteine pro-drug, on teratogenicity of 5-fluorouracil in mice.
Embryotoxicity and teratogenicity of 5-fluorouracil (5-FU) and modulation of its effect by L-2-oxothiazolidine-4-carboxylate (OTC), a cysteine pro-drug, were evaluated in mice. Pregnant ICR mice were intraperitoneally (i.p.) injected with 25 mg/kg of 5-FU on day 11 of gestation (vaginal plug = day 0). Mice were pretreated i.p. with 950 mg/kg of OTC 4 hours before dosing with 5-FU. Dams were killed on day 17 of gestation. Fetuses were examined for external malformations, especially limb malformations. Pretreatment with OTC decreased the frequency and severity of oligodactyly induced by 5-FU, although the differences were not significant statistically. There was little difference in either liver glutathione levels, or body weight gain during gestation of dams between the 5-FU group and the 5-FU plus OTC group. Fetal mortality and fetal weight of the group treated with 5-FU alone were comparable with those of the group pretreated with OTC. In the present study, teratogenicity of 5-FU seemed to be slightly mitigated with OTC pretreatment.
Naya
M
M
Kyowa Toxicological Research Laboratories, Yamaguchi, Japan.
Noguchi
M
M
Mataki
Y
Y
Deguchi
T
T
Yasuda
M
M
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003553:Cystine / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D017880:Limb Deformities, Congenital; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011761:Pyrrolidonecarboxylic Acid; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines
D013844:Thiazoles; D053778:Thiazolidines; D003553:Cystine; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid; D005472:Fluorouracil; C029536:2-oxothiazolidine-4-carboxylic acid